title: Comparative safety of benzodiazepines and opioids among veterans affairs patients with posttraumatic stress disorder.
abstract: OBJECTIVE
  Although Veterans Affairs (VA) patients with posttraumatic stress disorder (PTSD) are prescribed benzodiazepines and opioids in addition to recommended pharmacotherapies, little is known about the safety of these medications. This study compared the 2-year incidence of adverse events among VA patients with PTSD exposed to combinations of selective serotonin reuptake inhibitors (SSRIs) or serotonin/norepinephrine reuptake inhibitors (SNRIs), benzodiazepines, and opioids.
  
  
  METHODS
  This retrospective cohort study used VA administrative data from 2004 to 2010 to identify and follow 5236 VA patients with PTSD with new episodes of (1) SSRIs/SNRIs only; (2) concurrent SSRIs/SNRIs and benzodiazepines; and (3) concurrent SSRIs/SNRIs, benzodiazepines, and opioids. Outcome measures were the 2-year incidence and adjusted hazard ratios (AHR) of mental health and medicine/surgery hospitalizations, emergency department visits, harmful events (eg, injuries and death), and any adverse event after adjustment for demographics, clinical covariates, and adverse event history.
  
  
  RESULTS
  Compared with SSRIs/SNRIs only, the adjusted risk of mental health hospitalizations (AHR: 1.87; 95% confidence interval [CI]: 1.37-2.53) was greater among patients prescribed SSRIs/SNRIs and benzodiazepines concurrently. The AHR of mental health hospitalizations (AHR: 2.00; 95% CI: 1.35-2.98), medicine/surgery hospitalizations (AHR: 4.86; 95% CI: 3.30-7.14), emergency department visits (AHR: 2.01; 95% CI: 1.53-2.65), any harmful event (2.92; 95% CI: 2.21-3.84), and any adverse event (AHR: 2.65; 95% CI: 2.18-3.23) were all significantly greater among patients prescribed SSRIs/SNRIs, benzodiazepines, and opioids than among those prescribed SSRIs/SNRIs only.
  
  
  CONCLUSIONS
  Concurrently prescribing SSRIs/SNRIs, benzodiazepines, and opioids among patients with PTSD is associated with adverse events. Although efforts are warranted to monitor patients who are prescribed combinations of these medications to prevent adverse events, these results should be interpreted with caution until they are replicated.
authors.affiliation: From the Health Services Research & Development (EJH, CAM, JG, DRK), Seattle, WA; Center of Excellence in Substance Abuse Treatment and Education (EJH, CAM, AJS, DRK), VA Puget Sound Health Care System, Seattle, WA; Department Psychiatry and Behavioral Sciences (EJH, AJS, DRK), University of Washington, Seattle; and Department of Educational Psychology (ZEI), University of Utah, Salt Lake City, UT.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Hawkins
authors.forename: Carol A
authors.initials: CA
authors.lastname: Malte
authors.forename: Joel
authors.initials: J
authors.lastname: Grossbard
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Saxon
authors.forename: Zac E
authors.initials: ZE
authors.lastname: Imel
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Kivlahan
mesh_terms: D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects; D001569:Benzodiazepines / Q000008:administration & dosage / Q000009:adverse effects; D004347:Drug Interactions; D016903:Drug Monitoring / Q000379:methods; D064420:Drug-Related Side Effects and Adverse Reactions / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control; D005260:Female; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D008297:Male; D008875:Middle Aged; D011619:Psychotropic Drugs / Q000008:administration & dosage / Q000009:adverse effects; D012189:Retrospective Studies; D012307:Risk Factors; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D013313:Stress Disorders, Post-Traumatic / Q000188:drug therapy / Q000453:epidemiology / Q000209:etiology / Q000523:psychology; D014481:United States / Q000453:epidemiology; D014728:Veterans / Q000523:psychology* / Q000706:statistics & numerical data; D058014:Veterans Health / Q000706:statistics & numerical data
chemical_list: D000701:Analgesics, Opioid; D001569:Benzodiazepines; D011619:Psychotropic Drugs; D017367:Selective Serotonin Reuptake Inhibitors